Chen X, Wei J, Li C, Pierson CR, Finlay JL, Lin J

Int J Oncol 52 571-578 02/01/2018

Abstract

Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL‑6) have tumor-promoting activity and are associated with poor survival outcomes in many cancers. Additionally, the IL‑6/GP130/STAT3 axis has been widely studied due to its pivotal role in tumor development and maintenance in a number of tissue types, including the cerebellum. However, the connection between IL‑6 signaling and medulloblastoma progression is largely unexplored. In the present study, we observed that IL‑6 induced medulloblastoma cell viability, cell proliferation and glycolysis. Furthermore, it also upregulated the expression of phosphorylated STAT3, indicating that the IL‑6/GP130/STAT3 pathway plays a central role in medulloblastoma. The FDA-approved drug bazedoxifene, a blocker of the formation of the hexameric IL‑6/IL‑6R/GP130 complex, was re-purposed in this study to inhibit the IL‑6/GP130/STAT3 signaling pathway. Bazedoxifene not only inhibited IL‑6 mediated cell viability and cell proliferation, and increased phosphorylated STAT3 expression, but it also decreased cell glycolysis, demonstrating a certain level of therapeutic efficacy in vitro. Collectively, our findings offer new insight into the molecular mechanism underlying the biological aggressiveness of medulloblastoma, the roles of IL‑6 in these processes and a possible efficacious adjuvant therapy for medulloblastoma.